Chronic angiotensin (1–7) injection accelerates STZ-induced diabetic renal injury
Abstract
Aim: The renin-angiotensin system (RAS) plays a critical role in blood pressure control and body fluid and electrolyte homeostasis. In the past few years, angio-tensin (Ang) (1–7) has been reported to counteract the effects of Ang II and was even considered as a new therapeutical target in RAS. The present study aimed to investigate the effect of Ang (1–7) administration on a diabetic animal model and the modulation on local RAS.
Methods: Streptozotocin (STZ) injection-induced diabetic rats were used in the experiment. The animals were divided into 3 groups: (1) control; (2) STZ-induced diabetes; and (3) STZ-induced diabetes with chronic Ang (1–7) treatment [D+Ang(1–7)]. In the D+Ang(1–7) group, a dose of 25 μg·kg−1·h−1 of Ang (1–7) was continually injected through the jugular vein by embedding mini-osmotic pump for 6 weeks. Plasma glucose, ratio of kidney to body weight, and 24 h urine protein and serum creatinine were monitored by conventional measurement. Plasma and renal Ang II levels were measured by radioimmunoassay. Ang-converting enzyme (ACE), ACE2, Ang II type 1 (AT1) receptor, Ang II type 2 (AT2) receptor, Ang (1–7) Mas receptor, and TGF-β1 mRNA levels were measured by real time PCR; ACE, ACE2, and TGF-β1 protein levels were analyzed by Western blotting.
Results: The renal function of diabetic rats was significantly retrogressed when compared with that of control rats. After the treatment by constant Ang (1–7) vein injection for 6 weeks, renal function was found to be even worse than diabetic rats, and both TGF-β1 mRNA and protein levels were elevated in the D+Ang(1–7) group compared with the diabetic rats. The real-time PCR result also showed an increase in ACE mRNA expression and decrease in ACE2 mRNA level in the D+Ang(1–7) group when compared with diabetic rats. The number of AT1 receptors increased in the Ang (1–7)-injected group, while the number of AT2 and Mas receptors decreased.
Conclusion: Exogenous Ang (1–7) injection did not ameliorate STZ-induced diabetic rat renal injury; on the contrary, it accelerated the progressive diabetic nephropathies.
Keywords:
Methods: Streptozotocin (STZ) injection-induced diabetic rats were used in the experiment. The animals were divided into 3 groups: (1) control; (2) STZ-induced diabetes; and (3) STZ-induced diabetes with chronic Ang (1–7) treatment [D+Ang(1–7)]. In the D+Ang(1–7) group, a dose of 25 μg·kg−1·h−1 of Ang (1–7) was continually injected through the jugular vein by embedding mini-osmotic pump for 6 weeks. Plasma glucose, ratio of kidney to body weight, and 24 h urine protein and serum creatinine were monitored by conventional measurement. Plasma and renal Ang II levels were measured by radioimmunoassay. Ang-converting enzyme (ACE), ACE2, Ang II type 1 (AT1) receptor, Ang II type 2 (AT2) receptor, Ang (1–7) Mas receptor, and TGF-β1 mRNA levels were measured by real time PCR; ACE, ACE2, and TGF-β1 protein levels were analyzed by Western blotting.
Results: The renal function of diabetic rats was significantly retrogressed when compared with that of control rats. After the treatment by constant Ang (1–7) vein injection for 6 weeks, renal function was found to be even worse than diabetic rats, and both TGF-β1 mRNA and protein levels were elevated in the D+Ang(1–7) group compared with the diabetic rats. The real-time PCR result also showed an increase in ACE mRNA expression and decrease in ACE2 mRNA level in the D+Ang(1–7) group when compared with diabetic rats. The number of AT1 receptors increased in the Ang (1–7)-injected group, while the number of AT2 and Mas receptors decreased.
Conclusion: Exogenous Ang (1–7) injection did not ameliorate STZ-induced diabetic rat renal injury; on the contrary, it accelerated the progressive diabetic nephropathies.